V.N.PrilepskayaV.N.Prilepskaya, А.А., А.А.KuzeminKuzemin,,

Т.А.Т.А.NazarenkoNazarenko, Т.М., Т.М.AstahovaAstahova

Research Centre of ObstetricsResearch Centre of Obstetrics, , Gynecology Gynecology & Perinatology, Moscow& Perinatology, Moscow

Mifepriston in emergencyMifepriston in emergencycontraceptioncontraception

Main directions in the study of Main directions in the study of emergency contraception:emergency contraception:

Creation of the International Consortium on Creation of the International Consortium on Emergency ContraceptionEmergency Contraception

Enhancement of the WHO studies on that Enhancement of the WHO studies on that themetheme

Study of efficacy and comparison of different Study of efficacy and comparison of different methods (Youzpe method, levonorgestrel and methods (Youzpe method, levonorgestrel and mifepriston in different doses)mifepriston in different doses)

Prolongation of an interval after an Prolongation of an interval after an unprotected sex unprotected sex ((from from 72 72 ttо 120 о 120 hrshrs))

Three regimens have been studied for Three regimens have been studied for emergency contraception emergency contraception

Randomized double blind study in Randomized double blind study in 15 15 family planning family planning clinics in clinics in 10 10 countriescountries 4136 4136 healthy women with healthy women with regular menstrual cycleregular menstrual cycle).).

Single dose of levonorgestrel Single dose of levonorgestrel – 1,5 м– 1,5 мggTwo doses of levonorgestrel with an Two doses of levonorgestrel with an

interval of interval of 1212 hrs hrs Single dose of Mifepriston Single dose of Mifepriston – 10– 10mgmg

ConclusionConclusion

««All three regimens are very All three regimens are very efficient for emergency efficient for emergency contraception and prevent a high contraception and prevent a high per cent of pregnancies if taken per cent of pregnancies if taken during the first during the first 55 days days»»

Helene von Hertzen et al. Lancet 2002, 360:1803-10Helene von Hertzen et al. Lancet 2002, 360:1803-10

ММifepristonifepriston

Synthetic steroidSynthetic steroid, , derivative of nortetisteron derivative of nortetisteron with antigestagen activitywith antigestagen activity..

Main indicationMain indication is medical abortion is medical abortion

Additional indicationsAdditional indications:: Treatment of uterine leyomyomaTreatment of uterine leyomyoma Emergency contraceptionEmergency contraception

MifepristonMifepriston ( (tabletstablets 10 м 10 мg,g, М Мir-Pharmir-Pharm))

As a means of emergency As a means of emergency contraception mifepriston was contraception mifepriston was registered after clinical trials and was registered after clinical trials and was approved for clinical practice in Russia approved for clinical practice in Russia inin 2004 2004

ObjectivesObjectives

To assess efficacy and safety of To assess efficacy and safety of low-dose mifepristonelow-dose mifepristone(10мг) (10мг) as a as a method of emergency contraceptionmethod of emergency contraception

Clinical TrialsClinical Trials

Clinical trials on these indications were carried Clinical trials on these indications were carried out for the first time at the Research center of out for the first time at the Research center of Obstetrics, Gynecology & Perinatology of the Obstetrics, Gynecology & Perinatology of the Russian Academy of Medical Sciences, Russia Russian Academy of Medical Sciences, Russia

Coordinator of the trial - Member of the Academy Coordinator of the trial - Member of the Academy of the Medical Sciences Vladimir I. Kulakovof the Medical Sciences Vladimir I. Kulakov

A total ofA total of 30 30 women were included in this trial women were included in this trial

Inclusion criteria:Inclusion criteria:

Unprotected sex not more than Unprotected sex not more than 72 72 hrs thrs tоо visitvisit

Reproductive ageReproductive age Regular menstrual cycle during the last Regular menstrual cycle during the last

three monthsthree months No of psychic pathologyNo of psychic pathology Patient informed consentPatient informed consent

Exclusion criteria:Exclusion criteria:

Using of other contraceptive methodsUsing of other contraceptive methodsPostpartum periodPostpartum periodAdrenal insufficiencyAdrenal insufficiencyThromboses in the medical/family historyThromboses in the medical/family historySevere diabetes mellitusSevere diabetes mellitusGenital tumorGenital tumor

Indications for emergency Indications for emergency contraceptioncontraception

Absence of any contraception in regular Absence of any contraception in regular sexual lifesexual life (25) (25)

Failure of condomFailure of condom (2) (2) IUD expulsion during the cycle of the studyIUD expulsion during the cycle of the study

(2)(2)Sexual abuseSexual abuse (1) (1)Age fromAge from 18 18 to to 33 33 yearsyears, , mean agemean age 23,8+ 23,8+/-/-

1,71,7 years years

Methods of studyMethods of study

ClinicalClinical ( (medical history, examinations etcmedical history, examinations etc.).) Questionnaire Questionnaire Blood/urine testsBlood/urine tests,, biochemical tests biochemical tests Bacterioscopy of vaginal dischargeBacterioscopy of vaginal discharge Tests for genital infections, HIVTests for genital infections, HIV Sonography of pelvis organs with Doppler Sonography of pelvis organs with Doppler

modesmodes HCG test in bloodHCG test in blood Progesterone test in bloodProgesterone test in blood

Study design included four Study design included four visits:visits:

ScreeningScreening 7-8th days after the intended menstrual 7-8th days after the intended menstrual

period period 7-87-8 th days of the following menstrual th days of the following menstrual

periodperiod Two months later the Two months later the 3-3-rdrd visitvisit

No pregnanciesNo pregnancies

А) А) verified by sonographyverified by sonography

В) В) verified by HCGverified by HCG

Basic criteriaBasic criteria - a number of - a number of pregnancies/ number of women using pregnancies/ number of women using MifepristonMifepriston

Parameters of efficiencyParameters of efficiency

FINDINGS:FINDINGS:

No No pregnanciespregnancies in in

3030 patients patients

Results:Results:

Side effects: long Side effects: long ((in average up to in average up to 4646 days days) ) or postponed cycles or postponed cycles - 34-36 - 34-36 days - indays - in 5 (16%) 5 (16%) patients onpatients on 2 2 –– 3 3 visits visits

Cycle was regular in all patients - by the Cycle was regular in all patients - by the 4 4 visit visit

None of any other side effectsNone of any other side effects

By the 4By the 4thth visit all 300 patients had regular visit all 300 patients had regular cyclescycles

1visit 2visit 3visit 4visit

28-3028-30

40-4640-46

34-3634-36

28-3028-30

Nam

ber

of

day

sN

amb

er o

f d

ays

Remote results of examination Remote results of examination (2-3 months after the 3 visit)(2-3 months after the 3 visit)

Regular menstrual cycle was in all patientsRegular menstrual cycle was in all patientsMean duration of mensyrual cycle of 28,1+/-3,2 daysMean duration of mensyrual cycle of 28,1+/-3,2 daysMean duration of menstruation 5,4+/-0,7Mean duration of menstruation 5,4+/-0,7

ConclusionConclusion

Results of the study testify of the Results of the study testify of the following:following:

High efficacy of Mifepriston in a single High efficacy of Mifepriston in a single dose taken during 72 hrs as a method of dose taken during 72 hrs as a method of emergency contraceptionemergency contraception

Its good toleranceIts good toleranceNormalizations of cycles in due timeNormalizations of cycles in due time

ConclusionConclusion

««Mifepriston delayed ovulation Mifepriston delayed ovulation that means prolonged cycle that means prolonged cycle and delayed of following and delayed of following menstrual cyclemenstrual cycle»»

Drawbacks:Drawbacks:

1.1. Small number of casesSmall number of cases

2.2. No of control groupNo of control group

Further investigationsFurther investigations

Comparison of Mifepriston effect in the Comparison of Mifepriston effect in the dose of dose of 10 м10 мgg in different regimens of in different regimens of useuse: 72 : 72 and and 120 120 hrs after unprotected hrs after unprotected sexsex

Intended designIntended design: 150: 150 patients in each patients in each groupgroup

Thank you for your attentionThank you for your attention